Cost evaluation of PAGE-B risk score guided HCC surveillance in patients with treated chronic hepatitis B.
Ontology highlight
ABSTRACT: Background
The PAGE-B score (Platelet Age GEnder-HBV) selects chronic hepatitis B (cHB) patients showing no relevant 5-year risk for hepatocellular carcinoma (HCC). We, therefore, explored potential cost reduction following the introduction of a PAGE-B tailored ultrasound screening in a single center cohort of cHB patients receiving stable antiviral therapy.Methods
cHB patients attending throughout the year 2018 were documented. Patients eligible for PAGE-B score were classified into high (≥18 points), intermediate (10-17 points) and low (≤9 points) HCC risk groups. Patients of the low HCC risk group could postpone HCC screening to reduce HCC screening expenses. Full costs for hepatic ultrasound were assessed.Results
Throughout the year cHB patients (n = 607) attended our clinic, which included PAGE-B eligible patients (n = 227, 37.4%) of whom n = 94 (15.8%) were allocated to the low HCC risk group. Sonographic HCC screening during a median exam time of 12.4 min (IQR 9.2-17.2) resulted in total costs of 22.82 Euro/exam. Additional opportunistic expenses caused by patient's lost earnings or productivity were 15.6-17.5 €/exam and 26.7 €/exam, respectively. Following a PAGE-B tailored HCC screening at our institution annual full costs for cHB patients could be reduced by 15.51%, which equals a cost reduction by 1.91% for our total sonography unit. In comparison, 1.35% up to 7.65% of HBV-infected patients of Caucasian descent could postpone HCC screening according to population-based estimates from Germany.Conclusions
PAGE-B risk score adapted screening for HCC is an efficient and cost neutral tool to reduce costs for sonography in Caucasian patients with chronic hepatitis B receiving antiviral treatment.
SUBMITTER: Sprinzl MF
PROVIDER: S-EPMC8379870 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
| S-EPMC8046670 | biostudies-literature
Project description:Objective:HCV clearance by current antiviral therapies improves clinical outcomes but falls short in eliminating the risk for hepatocellular carcinoma (HCC) emergence. As the HCC immune surveillance establishment is vital for the control of neoplastic development and growth, we investigated its correlation with on-/post-treatment HCC emergence, and further analyzed the influence of viral eradication on this setup in patients with HCV-related liver cirrhosis. Design:PBMC isolated at baseline and longitudinally during therapy were analyzed for tumor-associated antigen (TAA)-specific CD8+ T cell responses against glypican-3 overlapping peptides in vitro using high-definition flow cytometry. Multianalyte profiling of fifty soluble inflammatory mediators (SIM) in the plasma was also performed using Luminex-based multiplex technology. Results:Cirrhosis patients were characterized by an altered profile of distinct SIMs at baseline. At this time point, immune-surveilling T cells targeting specific HCC-associated antigens were readily detectable in HCV-free cirrhosis patients whilst being rather weak in such patients who further developed HCC upon virus eradication. Therapy-induced cure of HCV infection analogously reduced the strength of the prevailing HCC immune surveillance machinery, particularly by CD8+ T cells in cirrhosis patients. These results were further validated by T cell reactivities to six immuno-dominant HCC-associated HLA-A2-restricted epi-topes. Further, we demonstrated that this phenomenon was likely orchestrated by alterations in SIMs - with evidence of IL-12 being a major culprit. Conclusion:Given the relationship between the baseline HCC-specific immune surveilling T cell responses and therapy-associated HCC emergence, and the impact of HCV clearance on its strength and magnitude, we recommend a continued HCC screening in cirrhotic HCV patients despite HCV resolution.
| S-EPMC6388568 | biostudies-literature
Project description:BackgroundChina has the highest prevalence of hepatitis B virus (HBV) infection worldwide. Universal HBV screening might enable China to reach the WHO 2030 target of 90% diagnostics, 80% treatment, and 65% HBV-related death reduction, and eventually elimination of viral hepatitis. We evaluated the cost-effectiveness of implementing universal HBV screening in China and identified optimal screening strategies.MethodsWe used a Markov cohort model, inputting parameters based on data from previous studies and public databases, to assess the cost-effectiveness of four HBV serological screening strategies in China in different screening scenarios. We simulated universal screening scenarios in 15 adult age groups between 18 and 70 years, with different years of screening implementation (2021, 2026, and 2031) and compared to the status quo (ie, no universal screening); in total, we investigated 180 different screening scenarios. We calculated the incremental cost-effectiveness ratio (ICER) between the different screening strategies and the status quo (current screening strategy). We performed probabilistic and one-way deterministic sensitivity analyses to assess the robustness of our findings.FindingsWith a willingness-to-pay level of three times the Chinese gross domestic product (GDP) per capita (US$30 828), all universal screening scenarios in 2021 were cost-effective compared with the status quo. The serum HBsAg/HBsAb/HBeAg/HBeAb/HBcAb (five-test) screening strategy in people aged 18-70 years was the most cost-effective strategy in 2021 (ICER $18 295/quality-adjusted life-years [QALY] gained). This strategy remained the most cost-effective, when the willingness-to-pay threshold was reduced to 2 times GDP per capita. The two-test strategy for people aged 18-70 years became more cost-effective at lower willingness-to-pay levels. The five-test strategy could prevent 3·46 million liver-related deaths in China over the lifetime of the cohort. It remained the most cost-effective strategy when implementation was delayed until 2026 (ICER $20 183/QALY) and 2031 (ICER $23 123/QALY). Screening young people (18-30 years) will no longer be cost-effective in delayed scenarios.InterpretationThe five-test universal screening strategy in people aged 18-70 years, implemented within the next 10 years, is the optimal HBV screening strategy for China. Other screening strategies could be cost-effective alternatives, if budget is limited in rural areas. Delaying strategy implementation reduces overall cost-effectiveness. Early screening initiation will aid global efforts in achieving viral hepatitis elimination.FundingNational Natural Science Foundation of China.
| S-EPMC8789560 | biostudies-literature
Project description:BackgroundNo consensus exists on screening to detect the estimated 2 million Americans unaware of their chronic hepatitis C infections. Advisory groups differ, recommending birth-cohort screening for baby boomers, screening only high-risk individuals, or no screening. We assessed one-time risk assessment and screening to identify previously undiagnosed 40-74 year-olds given newly available hepatitis C treatments.Methods and findingsA Markov model evaluated alternative risk-factor guided and birth-cohort screening and treatment strategies. Risk factors included drug use history, blood transfusion before 1992, and multiple sexual partners. Analyses of the National Health and Nutrition Examination Survey provided sex-, race-, age-, and risk-factor-specific hepatitis C prevalence and mortality rates. Nine strategies combined screening (no screening, risk-factor guided screening, or birth-cohort screening) and treatment (standard therapy-peginterferon alfa and ribavirin, Interleukin-28B-guided (IL28B) triple-therapy-standard therapy plus a protease inhibitor, or universal triple therapy). Response-guided treatment depended on HCV genotype. Outcomes include discounted lifetime costs (2010 dollars) and quality adjusted life-years (QALYs). Compared to no screening, risk-factor guided and birth-cohort screening for 50 year-olds gained 0.7 to 3.5 quality adjusted life-days and cost $168 to $568 per person. Birth-cohort screening provided more benefit per dollar than risk-factor guided screening and cost $65,749 per QALY if followed by universal triple therapy compared to screening followed by IL28B-guided triple therapy. If only 10% of screen-detected, eligible patients initiate treatment at each opportunity, birth-cohort screening with universal triple therapy costs $241,100 per QALY. Assuming treatment with triple therapy, screening all individuals aged 40-64 years costs less than $100,000 per QALY.ConclusionsThe cost-effectiveness of one-time birth-cohort hepatitis C screening for 40-64 year olds is comparable to other screening programs, provided that the healthcare system has sufficient capacity to deliver prompt treatment and appropriate follow-on care to many newly screen-detected individuals.
| S-EPMC3606430 | biostudies-literature
Project description:The phase 3 trial, Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol-2 (RESPOND-2), demonstrated that the addition of boceprevir (BOC) to peginterferon-ribavirin (PR) resulted in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection as compared with PR alone. We evaluated the cost-effectiveness of treatment with BOC in previously treated patients with chronic hepatitis C in the United States using treatment-related data from RESPOND-2 and PROVIDE studies.We developed a Markov cohort model to project the burden of HCV disease, lifetime costs, and quality-adjusted life-years associated with PR and two BOC-based therapies-response-guided therapy (BOC/RGT) and fixed-duration therapy for 48 weeks (BOC/PR48). We estimated treatment-related inputs (efficacy, adverse events, and discontinuations) from clinical trials and obtained disease progression rates, costs, and quality-of-life data from published studies. We estimated the incremental cost-effectiveness ratio (ICER) for BOC-based regimens as studied in RESPOND-2, as well as by patient's prior response to treatment and the IL-28B genotype.BOC-based regimens were projected to reduce the lifetime incidence of liver-related complications by 43% to 53% in comparison with treatment with PR. The ICER of BOC/RGT in comparison with that of PR was $30,200, and the ICER of BOC/PR48 in comparison with that of BOC/RGT was $91,500. At a willingness-to-pay threshold of $50,000, the probabilities of BOC/RGT and BOC/PR48 being the preferred option were 0.74 and 0.25, respectively.In patients previously treated for chronic HCV genotype-1 infection, BOC was projected to increase quality-adjusted life-years and reduce the lifetime incidence of liver complications. In addition, BOC-based therapies were projected to be cost-effective in comparison with PR alone at commonly used willingness-to-pay thresholds.
| S-EPMC3820000 | biostudies-literature
Project description:BackgroundVietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years.MethodsWe plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data.DiscussionThe present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries.Trial registrationName of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.
| S-EPMC10506187 | biostudies-literature
Project description:We attempted to development prediction methods for hepatocellular carcinoma (HCC) in chronic hepatitis C patients who have been successfully treated by anti-viral therapy. 2565 miRNAs in 139 exosome specimens were analyzed.
2020-01-24 | GSE119159 | GEO
Project description:We attempted to development prediction methods for hepatocellular carcinoma (HCC) in chronic hepatitis C patients who have been successfully treated by anti-viral therapy. 2565 miRNAs in 43 liver tissues specimens were analyzed.
2020-01-24 | GSE119156 | GEO
Project description:Outside of expert centres, surveillance programmes for hepatocellular carcinoma (HCC) are not well executed. There are deficiencies in every stage of the process. Overcoming these obstacles is the most important method for improving surveillance. However, even if these obstacles were overcome, there would still be room for improvement. Assessing who is at risk of developing HCC remains incompletely validated. At present, risk scores have been developed for different causes of liver disease, but scores developed in different parts of the world for the same disease do not always agree. Furthermore, most scores stratify patients by risk but do not examine what level of risk should trigger surveillance. Which surveillance tools to use remains controversial - schemes have been proposed that use biomarkers alone, ultrasound alone, or a combination of both. However, the requisite level of test sensitivity that would be associated with high cure rates has not been defined, so at this point it is not clear whether surveillance requires both ultrasound and biomarkers, or whether the use of biomarkers alone is sufficient. Finally, surveillance should result in the identification of HCC at a very early stage. Diagnosing these lesions is difficult and optimal algorithms for lesions that are atypical on radiology have yet to be developed. Algorithms for the follow-up of abnormal biomarkers in the absence of ultrasound have also not been developed yet.
| S-EPMC7005767 | biostudies-literature
Project description:HCV infection is a leading cause of chronic liver disease with long-term complications-extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital "Queen Joanna-ISUL" for 3-year period (2012-2014).It is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital "Queen Joanna-ISUL" for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy) were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF), hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal-Wallis, and Friedman tests were used for statistical processing.76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839) with an average cost per patient 4,577 BGN (€2,340). Statistically significant correlation was observed between the total cost per patient from the different payers' perspective and the Child-Pugh cirrhosis score.HCV-related cirrhosis is resource demanding and sets high direct medical costs as it is related with increased hospitalizations and complications acquiring additional treatment.
| S-EPMC5545579 | biostudies-other